Just What Is a Biologic, Anyway? : Part 2

by Food and Drug Administration (FDA)

(Page 2 of 2)

The monoclonal antibody is chemically modified so it can bind to radioactive Indium 111, with which it is mixed just before it is injected into the patient. Special cameras collect images, seen as "hot spots," indicating where the radiolabeled antibody has bound to the protein and where tumors may be located.

The imaging agent is licensed for use in patients with known ovarian or colorectal cancer in whom recurring or spreading cancer is suspected. It may enable doctors to diagnose earlier small tumor deposits in the abdominal cavity in patients with recurring ovarian cancer. These are often missed by conventional tests.

Diagnostic testing with the new imaging product does not replace CT (computed tomography) scans and other standard tests but can be used with them. It is not effective as a screening test for ovarian or colorectal cancer.

Future Help?

Many scientists think cell therapy is one of the most promising new technologies under investigation. Genetic and cellular therapies "are possibly the future medical breakthrough therapies which use genetic engineering of human cells," Beatrice says.

For example, he explains, in the future, rather than injecting the missing clotting factor in a patient at frequent intervals, doctors might be able to remove appropriate cells, manipulate them genetically so they could make the missing factor themselves, and then reintroduce them into the patient's body.

One example of a cell therapy currently being tested is human ADA gene therapy. The National Institutes of Health's Clinical Center in Bethesda began testing this therapy Sept. 14, 1990, on a 4-year-old girl suffering from a deadly genetic disorder called severe combined immune deficiency.

Because of a tiny chemical error in her DNA, the child lacks a properly functioning gene for making an enzyme called adenosine deaminase (ADA). Without this enzyme, she became deficient in white blood cells called lymphocytes, which normally fight off all manner of chance infections.

In the gene therapy treatment currently being evaluated, some white blood cells are removed. In the laboratory, researchers install good copies of the ADA gene. Then the cells are put back into the child's circulating blood. In theory, as long as these gene- modified cells continue to function, they should provide the enzyme. (See "A New Era of Gene Therapy" in the December 1991 FDA Consumer.)

These investigational new therapies offer much promise but are not without risk. "The reviewers have to be mindful of all the possibilities for problems that could occur at any stage. And those sets of problems differ depending on the nature of the product," Beatrice says.

In the cell therapies, many of the biotech products employed are manufactured in continuous cell lines.

Products manufactured by using these cells must be highly purified to ensure they are not contaminated with viruses or proteins capable of transforming normal cells in the person who receives them.

Other Major Issues

According to Beatrice, some other major biologics issues include: continued assurance of the safety of the blood supply in the United States, upgrading and maintaining a scientifically based vaccine review program, keeping up with the new technology to ensure that the products, as well as the cell lines from which they're derived, are safe.

Of the blood program, Beatrice says, "We want to make sure that all the blood collected and used in this country is as safe as possible at all times and that the possibility for any contaminated blood is reduced to an absolute minimum — that's our ongoing concern."

FDA's vaccine review program is of particular importance, not just in this country but worldwide.

"We need to study combination vaccine products because you can't always get to the people as frequently [as necessary] and bring them back for shots of however many vaccines," he says.

"Combination vaccines will make possible fewer visits to the physician, but it's also necessary to make sure these combinations are effective and can withstand the conditions out in the field — for example, heat and humidity — if given in certain Third World countries."

He adds that the agency also has to have continuous assurance of the quality of vaccines for the population and their continued improvement.

Although new uses may be developed, biologics remain, at their root, the same today as they have always been: Derived from living material — plants, animals, humans, and microorganisms — and used to prevent, treat or cure human disease or injury.

How Biologics Are Regulated

The Virus-Toxin Law, enacted July 1, 1902, four years before the Food, Drug, and Cosmetic Act, brought biological products under federal regulatory control.

The Virus-Toxin Law specifies manufacturing, inspection, licensing, and labeling requirements with which a biological product manufacturer must comply.

The impetus for the law came from an accident with diphtheria antitoxin that killed several St. Louis children earlier that year. The children died because the horse's blood used in producing the diphtheria antitoxin had been contaminated with tetanus bacteria. In 1944, the law was revised and incorporated into the Public Health Service Act.

The National Institutes of Health maintained regulatory control of biologics until 1972, when its Division of Biologics Standards was transferred to FDA. The division was later renamed the Center for Biologics Evaluation and Research. The transfer allowed a blending of the scientific and research expertise of NIH with the regulatory experience of FDA.

The stringent regulations governing biological products require the center to evaluate two major applications before any new product can be licensed. "We have to review at the same time the product license application — which is similar to a new drug application — and an establishment license application," FDA's Michael Beatrice says.

The establishment license application, which certifies that manufacturing facilities meet specific standards, is an "integral part of the biological product review process because of the need to maintain strict controls due to the sensitivity of products to their environment during manufacture," he says.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.